2-(P-Phenylazoanilino)quinolizinium bromide

ABSTRACT

2-(p-Phenylazoanilino)quinolizinium bromide is a useful antiinflammatory agent.

United States Patent [191 Alaimo et a].

[ Aug. 12, 1975 PHENYLAZOANILINO )QUINOLIZINIUM BROMIDE [75] Inventors: Robert J. Alaimo; Marvin M.

Goldenberg, both of Norwich, N.Y.

[73] Assignee: Morton-Norwich Products, Inc., Norwich, N.Y.

22 Filed: Dec. 26, 1973 21 Appl. N0.: 431,141

Related US. Application Data [62] Division of Ser. No. 278,618, Aug. 17, 1972, Pat. No,

[56] References Cited UNITED STATES PATENTS 2,725,376 11/1955 Brody ..260/155 2,742,457 4/1956 Rudner 260/156 3,519,615 7/1970 Wolfrum et 211.... 3,666,746 5/1972 Stanley et a1. 260/152 OTHER PUBLICATIONS Alaimo, Chemical Abstracts, Vol. 72, p. 414, No. 55286g, (1970).

Alaimo, J. Med. Chem., Vol. 13, No. 3, pp. 554-556,

Bohlmann et al., Ber. Deut. Chem. GeselL, Vol. 97, pp. 1619-1624, (1964).

Primary ExaminerFloyd D. Higel Attorney, Agent, or Firm-Anthony J. Franze [5 7] ABSTRACT 2-(p-Phenylazoanilino)quinolizinium bromide is a useful anti-inflammatory agent.

1 Claim, No Drawings 1 2-(P-PHENYLAZOANILINO)QUINOLIZINIUM BROMIDE This is a division of application 'Ser. No. 278,618, filed Aug. 17, 1972, and now U.S. Pat. No. 3,880,868.

This invention relates to Z-(substituted amino) 5 quinolizinium bromides and particularly to those of the formula:

wherein R is hydrogen or methyl; R is hydrogen or amino, and R is hydroxyethyl, 2,3-dihydroxypropyl, p-phenylazoanilino or m-trifluoromethylanilino.

The compounds of this invention possess marked anti-inflammatory activity. When administered perorally in aqueous suspension at a dose of 300 mg/kg to rats which thereafter receive a subplantar injection of 0.05 ml. of a 1% solution of carrageen (Viscarin in the hindfoot, edema of the foot is greatly reduced. They are thus useful agents in combatting swelling and edema in animal tissue.

The method which is currently preferred for the preparation of the compounds of this invention consists in bringing together 2-bromo-6-methylquinolizinium bromide or 2-bromoquinolizinium bromide and the appropriate amine in a suitable solvent such as ethanol or isopropanol preferably under the influence of heat.

In order that this invention may be understood by and readily available to those skilled in the art the following illustrative examples are supplied.

EXAMPLE I 2-[ 1-(2-Hydroxyethyl)hydrazino]-6- methylquinolizinium Bromide EXAMPLE ll 2-(2,3-Dihydroxypropylamino)quinolizinium Bromide To a solution of 2-bromoquinolizinium bromide (8.0 g, 0.03 mole) in ethanol (150 ml.) was added l-amino- 2,3-propanediol (4.0 g, 0.04 mole). The stirred mixture was boiled under reflux for 3 hours. Cooling of the reaction mixture in an ice bath along with vigorous scratching precipitated a dark redbrown solid. The product (5.0 g, 60%) was recrystallized from ethanol to provide salmon colored crystals which melted at 166-168.

Anal. Calcd. for C H BrN O C, 48.17; H, 5.05; Br, 26.71. Found: C, 48.42; H, 5.01; Br, 26.58,; 26.64.

EXAMPLE III 2-(p-Phenylazoanilino)quinolizinium Bromide To a solution of 2-bromoquinolizinium bromide (15.0 g, 0.05 mole) in isopropanol (300 ml.) was added p-phenylazoaniline (18.0 g, 0.09 mole). The stirred mixture was boiled under reflux for 4.0 hours. The reaction mixture was chilled in an ice bath and the solid was removed by filtration, providing 10.0 g. of maroon powder. The supernatant solution provided 9.0 g. additional reddish powder, making the total yield 19.0 g. Recrystallization from isopropanol/ethanol and again from ethanol/ether provided a rust-colored powder melting at 239-240.

Anal. Calcd. for C H BrN C, 62.23; H, 4.23; N, 13.95; Br, 19.72. Found: C, 61.94, 62.07; H, 4.23, 4.29; N, 13.65, 13.67; Br, 19.80, 19.67.

EXAMPLE 1V 2-(mTrifluoromethylanilino)quinolizinium Bromide To a solution of 2-bromoquinolizinium bromide (45 g, 0.15 mole) in ethanol (600 ml.) was added mtrifluoromethylaniline (50 g, 0.30 mole). The stirred mixture was boiled under reflux for 5 hours, then treated with Darco and filtered. The product was precipitated with ether. The crude product weighed 42 g. (76%). Recrystallization from isopropanol/ether provided material that melted at 229-230.

Anal. Calcd. for C H BrF N z C, 52.05; H, 3.28; N, 7.59. Found: C, 51.96; H, 3.25; N, 7.61.

What is claimed is:

l. The compound phenylazoanilino)quinolizinium bromide. 

1. THE COMPOUND 2-(P-PHENYLAZOANILINO)QUINOLUZIUM BROMIDE. 